Project Summary/Abstract Dysregulated immune responses are of central importance to the pathogenesis and expression of a wide spectrum of diseases that cause an immense burden of morbidity and mortality. The overall Aim of the training grant is to provide training for 3 pre-doctoral candidates, whose research will uncover pathogenic mechanisms of immune-mediated disease and facilitate transformative therapeutic approaches, consistent with the mission of the NIH. Candidates will be recruited from the Immunology Graduate Program (ImmGP) and the Medical Scientist Training Program at Cincinnati Children?s Hospital Medical Center (CCHMC) and the University of Cincinnati College of Medicine (UCCOM). Housed within CCHMC, one of the premiere pediatric research institutions in the US, the ImmGP attracts a strong and diverse pool of applicants. ImmGP students receive exemplary didactic instruction in immunology, research ethics, grant writing, and biostatistics. The training program will be led by a Director and Co-Director (Drs. Hildeman and Singh) who, along with 34 outstanding Training Faculty (TF), have significant experience in mentoring pre-doctoral students. Students will work with a diverse group of TF (comprised of MDs, MD/PhDs, and PhDs), from multiple departments at CCHMC/UCCOM, who share a collective focus on the mechanistic understanding of the immunologic basis of human disease. Students in this training program will be immersed in a distinctive environment: TF have well-funded research programs that span basic immunology to animal models of disease to clinical trials in human patients; CCHMC provides tremendous institutional resources (e.g., support for graduate education and faculty research, cutting- edge core facilities, unique patient cohorts); a collaborative research student exchange program with a German University and Research Institute provides a unique opportunity for international studies in immunology. Graduates of this program will be uniquely poised to bring innovations in immunology from the laboratory bench to the bedside and will be well-prepared for independent research careers.